The invention concerns a flow cell with a temperature-control chamber for holding a fluid, the temperature of which is to be controlled, whose boundary wall is formed at least partially by a thin foil for transferring heat between a temperature-control element and the fluid.
Microfluidic flow cells are being used to a greater and greater extent, especially as disposable products, for analytical and diagnostic purposes or in medicine for conditioning liquids before they are applied in the human body as well as for synthetic purposes. While the function of a flow cell can be limited to controlling the temperature of a fluid, temperature control devices are often only components of flow cells that have a much more extensive functionality. Especially for carrying out molecular genetic analyses, including PCR processes or other processes for nucleic acid amplification, the temperature-control function is extremely important because the amplification reaction requires constant or variable reaction temperatures above ambient temperature, typically between 30° C. and 95° C. The manufacture of temperature resistant flow cells with reproducible temperature-control characteristics that allow an especially rapid and homogeneous temperature transition between an active temperature-control element and the fluid whose temperature is to be controlled, especially the manufacture of such flow cells as inexpensive disposable products, presents significant problems.
U.S. Pat. No. 6,613,560 B1 discloses a flow cell with a temperature-control device of the aforementioned type. The flow cell is used for carrying out PCR processes. A reaction chamber for the PCR process simultaneously serves as the temperature-control chamber. The temperature-control chamber is bounded by a recess in a substrate and by a thin, heat-transmitting foil of the type mentioned above, which covers the recess. A disadvantage for the temperature-control process is the low thermal conductivity of plastics, for which reason foils with a low film thickness in the range of 50-200 μm are preferred. The fabrication, handling, and assembly of such thin foils is very complicated. It is a disadvantage that the cover foil does not form an exactly planar surface due to its low mechanical stiffness. Likewise, thermal and mechanical effects occurring during the assembly of the foil by adhesive or welding processes can easily lead to deformations of the foil and thus to deviations from the plane on the order of a few 10-100 μm. This makes it more difficult to introduce heat by pressing a temperature-control element against it; above all, air gaps left in the foil impair heat transmission and prevent rapid equalization between the temperature of the temperature-control element and the temperature of the fluid in the temperature-control chamber, especially its even heating or cooling. It is not possible to realize reproducible temperature-control characteristics, especially under the conditions of inexpensive mass production of this flow cell.